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Annual Results 2017 & Business Update
13 April 2018
Disclaimer
These slides and the accompanying oral presentation contain forward-looking statements and information. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from those anticipated by such statements. The use of words such as “may”, “might”, “will”, “should”, “could”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “project”, “intend”, “future”, “potential” or “continue”, and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding (i) the initiation, timing, cost, progress and results of our preclinical and clinical studies and our research and developmentprograms, (ii) our ability to advance product candidates into, and successfully complete, clinical studies, (iii) the timing or likelihood of regulatory filings and approvals, (iv) our ability to develop, manufacture and commercialize our product candidates and to improve the manufacturing process, (v) the rate and degree of market acceptance of our product candidates, (vi) the size and growth potential of the markets for our product candidates and our ability to serve those markets, and (vii) our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates, are forward looking. All forward-looking statements are based on current estimates, assumptions and expectations by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. This presentation is not, and nothing in it should be construed as, an offer, invitation or recommendation in respect of our securities, or an offer, invitation or recommendation to sell, or a solicitation of an offer to buy, any of our securities in any jurisdiction. Neither this presentation nor anything in it shall form the basis of any contract or commitment. This presentation is not intended to be relied upon as advice to investors or potential investors and does not take into account the investment objectives, financial situation or needs of any investor.
2
HIGHLIGHTS - Operational
• Filed Marketing Authorization Application with the European Medicines Agency for ATIR101 in blood cancers
• Submitted responses to the EMA to enable a conditional marketing approval from the European Commission - potentially allowing an opinion from the EMA in Q4 2018
• Received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. FDA for ATIR101
• First patient enrolled in Phase 3 trial for ATIR101 in adult patients with blood cancer
• Leased existing commercial manufacturing facility in The Netherlands
• Strengthened Organization and Supervisory Board
3
HIGHLIGHTS – Financial
• Raised more than EUR 60 million in equity and debt since June 2017
• End of March 2018: EUR 47.7 million cash
4
2017 2016 Change
Total revenue and other income - - -
Total operating expenses (16.1) (11.4) (4.7)
Research and development (11.2) (8.2) (3.0)
General and administrative (4.9) (3.2) (1.7)
Operating result (16.1) (11.4) (4.7)
Net financial result (0.9) (3.4) 2.5
Net result (17.0) (14.8) (2.2)
Net operating cash flow (15.9) (14.3) (1.6)
Cash position at end of year 29.9 14.6 15.3
Equity 15.9 9.4 6.5
Earnings per share before dilution (EUR) (1.14) (1.08) (0.06)
(Amounts in EUR million, except per share data)
ATIR Regulatory Status
5
Product Pre-ClinicalPhase
IPhase
IIPhase
III Filing CatalystsCommercial
Rights
ATIR101(Europe)
- CHMP Opinion 4Q18
- EU Launch 2H19
ATIR101(USA)
- Phase III (interim) read outOrphan Drug & RMAT Designations
Orphan Drug Designation
The very first cell transplant method: allogeneic HSCT
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT):
• Curative intent: replace disease blood/immune system with healthy one from donor
• Risk of Graft versus Host disease (GVHD): Donor immune system attacks the patient
• Mostly blood cancers (85%) and adults (82%)
6
Adoption of HSCT limited by high risk
Blood cancers: Only 20-30% long term GVHD-Free and Relapse-Free Survival (GRFS)
Inherited blood disorders or autoimmune disease: Risk of replacing chronic disease with (chronic) GVHD
HSCT: Strong growth, still large unmet need (U.S.)
7Source: CIBMTR 2017 Summary slides; Fuchs 2017; Gragert 2014; Besse 2015
Historical: Matched Related or Unrelated Donors• Donor availability 20-80% (due to
family size & genetic diversity)• Declining, despite unmet need
Emerging: Haploidentical or half matched donors• Donor availability >95%
(parents/children)• 32% compound annual growth• Made possible due to Post
Transplant Cyclophosphamide (PTCy) or ‘Baltimore’ protocol*
Unmet need: 13,000 per year (lack of matched donors)
* Cyclophosphamide (chemotherapy, days 3 and 5) & immunosuppressants to treat immediate attack from alloreactive haploidentical donor T-cells
Haploidentical donors
Matched Unrelated Donor (MUD; registries)
Matched Related Donors (MRD)
Kiadis: potential improvement vs. PTCy/Baltimore
8
Kiadis’ ATIR (add on to HSCT)
PTCy
Apheresis of patient and
donor
Central ATIR production,
5 day processConditioning of
patient
Apheresis of donor,
graft infusion
Engraftment of donor
stem cellsInfusion of
ATIR
14 days before HSCT ~30 days after HSCT Aims to prevent GVHD
& relapse
stem cells only
Conditioning of patient
Apheresis of donor,
graft infusion
Engraftment of donor
stem cells
stem cells + all T-cells
Chemo & immuno-
suppressants
Day 2 & 5 after HSCT Treats GVHD
HAPLOIDENTICAL HSCT
ATIR production: subset of T-cells that protect, but not attack
ATIRTM MANUFACTURING PROCESS
MANUFACTURING
Kiadis Pharma has established a GMP-compliant, manufacturing process that has been successfully transferred to three GMP-
manufacturing sites in North America and Europe. The Company is one of seven companies to have ever been issued an Advanced
Therapy Medicinal Product (ATMP) certif cate for manufacturing quality and non-clinical data by the European Medicines Agency
(EMA).
MARKET POTENTIAL
ATIR101 has the potential of providing life-saving products to ~19,000 blood cancer patients a year, with a substantial expanding
primary market and complementary product trends. The Company estimates that approximately 35% of patients who are eligible
for, and who are in urgent need of, HSCT will not f nd a matching donor in time. A partially matched (haploidentical) family donor,
however, will be available to over 95%. Recent developments in cell-based immunotherapy have resulted in approached which
may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then
be eligible for curative HSCT. The product may benef t from market exclusivity up to 10 years post launch in the EU and 7 years in
the US due to its orphan drug status.
ATIR101 AIMS TO ADDRESS THE RISKS ANS LIMITATIONS OF HSCT
Current sequence of options physicians will consider
Haploidentical donor + ATIR101
IdenticalSibling(SIB)
MatchedUnrelated
(MUD)
Haploidenticaldonor +
Cyclophosphamide*
Umbilical Cord Blood
(UCB)
Time to collect stem cells < 1 month < 1-2 months 3-6 months < 1 month 2-3 months
Donor availability >95% ≤ 25% 45-55% >95% Limited
Risk of life-threatening GVHD Low Low Moderate - High Moderate - High Moderate
Need for immune suppressants No Yes Yes Yes Yes
Risk of opportunistic infections Low Moderate Moderate Moderate - High High
Risk of relapse in leukemia Low High Moderate - High High High
* Often referred to as the Baltimore protocol. Treatment method was established at the John Hopkins Hospital, Baltimore, USA. (Luznik et al., Biol Blood Marrow
Transplant. 2008)
Source table: Company information, CIBMTR, 2014 and Defin
e
d He al th, 2013 commi ssi oned by the Co mp any .
Survey included 50 US and 50 EU physicians.
Step 1 (Day 1–4)
Patient cells
inactivated
by radiation
Healthy
donor
Patient
Immune cells are collected and mixed
Certain T-cells from the donor are activated by the
presence of the ‘foreign’ patient cells. If not eliminated,
these cells would cause GvHD in the patient
Step 3 (Day 5)
Mixture is exposed to light.
TH9402 is activated by light, causing the
‘stained’ GvHD-causing T-cells to self-destruct
The remaining product is infused back
and helps rebuild their immune system
to f ght infections and eliminate
remaining tumor cells
Final Step - Infusion of ATIR101Step 2 (Day 5)
TH9402 is introduced.
TH9402 is retained ONLY in the GvHD-causing T-cells
FEBRUARY 2017
donor
patient
ATIRTM MANUFACTURING PROCESS
MANUFACTURING
Kiadis Pharma has established a GMP-compliant, manufacturing process that has been successfully transferred to three GMP-
manufacturing sites in North America and Europe. The Company is one of seven companies to have ever been issued an Advanced
Therapy Medicinal Product (ATMP) certif cate for manufacturing quality and non-clinical data by the European Medicines Agency
(EMA).
MARKET POTENTIAL
ATIR101 has the potential of providing life-saving products to ~19,000 blood cancer patients a year, with a substantial expanding
primary market and complementary product trends. The Company estimates that approximately 35% of patients who are eligible
for, and who are in urgent need of, HSCT will not f nd a matching donor in time. A partially matched (haploidentical) family donor,
however, will be available to over 95%. Recent developments in cell-based immunotherapy have resulted in approached which
may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then
be eligible for curative HSCT. The product may benef t from market exclusivity up to 10 years post launch in the EU and 7 years in
the US due to its orphan drug status.
ATIR101 AIMS TO ADDRESS THE RISKS ANS LIMITATIONS OF HSCT
Current sequence of options physicians will consider
Haploidentical donor + ATIR101
IdenticalSibling(SIB)
MatchedUnrelated
(MUD)
Haploidenticaldonor +
Cyclophosphamide*
Umbilical Cord Blood
(UCB)
Time to collect stem cells < 1 month < 1-2 months 3-6 months < 1 month 2-3 months
Donor availability >95% ≤ 25% 45-55% >95% Limited
Risk of life-threatening GVHD Low Low Moderate - High Moderate - High Moderate
Need for immune suppressants No Yes Yes Yes Yes
Risk of opportunistic infections Low Moderate Moderate Moderate - High High
Risk of relapse in leukemia Low High Moderate - High High High
* Often referred to as the Baltimore protocol. Treatment method was established at the John Hopkins Hospital, Baltimore, USA. (Luznik et al., Biol Blood Marrow
Transplant. 2008)
Source table: Company information, CIBMTR, 2014 and Defin
e
d He al th, 2013 commi ssi oned by the Co mp any .
Survey included 50 US and 50 EU physicians.
Step 1 (Day 1–4)
Patient cells
inactivated
by radiation
Healthy
donor
Patient
Immune cells are collected and mixed
Certain T-cells from the donor are activated by the
presence of the ‘foreign’ patient cells. If not eliminated,
these cells would cause GvHD in the patient
Step 3 (Day 5)
Mixture is exposed to light.
TH9402 is activated by light, causing the
‘stained’ GvHD-causing T-cells to self-destruct
The remaining product is infused back
and helps rebuild their immune system
to f ght infections and eliminate
remaining tumor cells
Final Step - Infusion of ATIR101Step 2 (Day 5)
TH9402 is introduced.
TH9402 is retained ONLY in the GvHD-causing T-cells
FEBRUARY 2017
ATIRTM MANUFACTURING PROCESS
MANUFACTURING
Kiadis Pharma has established a GMP-compliant, manufacturing process that has been successfully transferred to three GMP-
manufacturing sites in North America and Europe. The Company is one of seven companies to have ever been issued an Advanced
Therapy Medicinal Product (ATMP) certif cate for manufacturing quality and non-clinical data by the European Medicines Agency
(EMA).
MARKET POTENTIAL
ATIR101 has the potential of providing life-saving products to ~19,000 blood cancer patients a year, with a substantial expanding
primary market and complementary product trends. The Company estimates that approximately 35% of patients who are eligible
for, and who are in urgent need of, HSCT will not f nd a matching donor in time. A partially matched (haploidentical) family donor,
however, will be available to over 95%. Recent developments in cell-based immunotherapy have resulted in approached which
may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then
be eligible for curative HSCT. The product may benef t from market exclusivity up to 10 years post launch in the EU and 7 years in
the US due to its orphan drug status.
ATIR101 AIMS TO ADDRESS THE RISKS ANS LIMITATIONS OF HSCT
Current sequence of options physicians will consider
Haploidentical donor + ATIR101
IdenticalSibling(SIB)
MatchedUnrelated
(MUD)
Haploidenticaldonor +
Cyclophosphamide*
Umbilical Cord Blood
(UCB)
Time to collect stem cells < 1 month < 1-2 months 3-6 months < 1 month 2-3 months
Donor availability >95% ≤ 25% 45-55% >95% Limited
Risk of life-threatening GVHD Low Low Moderate - High Moderate - High Moderate
Need for immune suppressants No Yes Yes Yes Yes
Risk of opportunistic infections Low Moderate Moderate Moderate - High High
Risk of relapse in leukemia Low High Moderate - High High High
* Often referred to as the Baltimore protocol. Treatment method was established at the John Hopkins Hospital, Baltimore, USA. (Luznik et al., Biol Blood Marrow
Transplant. 2008)
Source table: Company information, CIBMTR, 2014 and Defin
e
d He al th, 2013 commi ssi oned by the Co mp any .
Survey included 50 US and 50 EU physicians.
Step 1 (Day 1–4)
Patient cells
inactivated
by radiation
Healthy
donor
Patient
Immune cells are collected and mixed
Certain T-cells from the donor are activated by the
presence of the ‘foreign’ patient cells. If not eliminated,
these cells would cause GvHD in the patient
Step 3 (Day 5)
Mixture is exposed to light.
TH9402 is activated by light, causing the
‘stained’ GvHD-causing T-cells to self-destruct
The remaining product is infused back
and helps rebuild their immune system
to f ght infections and eliminate
remaining tumor cells
Final Step - Infusion of ATIR101Step 2 (Day 5)
TH9402 is introduced.
TH9402 is retained ONLY in the GvHD-causing T-cells
FEBRUARY 2017ATIRTM MANUFACTURING PROCESS
MANUFACTURING
Kiadis Pharma has established a GMP-compliant, manufacturing process that has been successfully transferred to three GMP-
manufacturing sites in North America and Europe. The Company is one of seven companies to have ever been issued an Advanced
Therapy Medicinal Product (ATMP) certif cate for manufacturing quality and non-clinical data by the European Medicines Agency
(EMA).
MARKET POTENTIAL
ATIR101 has the potential of providing life-saving products to ~19,000 blood cancer patients a year, with a substantial expanding
primary market and complementary product trends. The Company estimates that approximately 35% of patients who are eligible
for, and who are in urgent need of, HSCT will not f nd a matching donor in time. A partially matched (haploidentical) family donor,
however, will be available to over 95%. Recent developments in cell-based immunotherapy have resulted in approached which
may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then
be eligible for curative HSCT. The product may benef t from market exclusivity up to 10 years post launch in the EU and 7 years in
the US due to its orphan drug status.
ATIR101 AIMS TO ADDRESS THE RISKS ANS LIMITATIONS OF HSCT
Current sequence of options physicians will consider
Haploidentical donor + ATIR101
IdenticalSibling(SIB)
MatchedUnrelated
(MUD)
Haploidenticaldonor +
Cyclophosphamide*
Umbilical Cord Blood
(UCB)
Time to collect stem cells < 1 month < 1-2 months 3-6 months < 1 month 2-3 months
Donor availability >95% ≤ 25% 45-55% >95% Limited
Risk of life-threatening GVHD Low Low Moderate - High Moderate - High Moderate
Need for immune suppressants No Yes Yes Yes Yes
Risk of opportunistic infections Low Moderate Moderate Moderate - High High
Risk of relapse in leukemia Low High Moderate - High High High
* Often referred to as the Baltimore protocol. Treatment method was established at the John Hopkins Hospital, Baltimore, USA. (Luznik et al., Biol Blood Marrow
Transplant. 2008)
Source table: Company information, CIBMTR, 2014 and Defin
e
d He al th, 2013 commi ssi oned by the Co mp any .
Survey included 50 US and 50 EU physicians.
Step 1 (Day 1–4)
Patient cells
inactivated
by radiation
Healthy
donor
Patient
Immune cells are collected and mixed
Certain T-cells from the donor are activated by the
presence of the ‘foreign’ patient cells. If not eliminated,
these cells would cause GvHD in the patient
Step 3 (Day 5)
Mixture is exposed to light.
TH9402 is activated by light, causing the
‘stained’ GvHD-causing T-cells to self-destruct
The remaining product is infused back
and helps rebuild their immune system
to f ght infections and eliminate
remaining tumor cells
Final Step - Infusion of ATIR101Step 2 (Day 5)
TH9402 is introduced.
TH9402 is retained ONLY in the GvHD-causing T-cells
FEBRUARY 2017
`ATIRTM MANUFACTURING PROCESS
MANUFACTURING
Kiadis Pharma has established a GMP-compliant, manufacturing process that has been successfully transferred to three GMP-
manufacturing sites in North America and Europe. The Company is one of seven companies to have ever been issued an Advanced
Therapy Medicinal Product (ATMP) certif cate for manufacturing quality and non-clinical data by the European Medicines Agency
(EMA).
MARKET POTENTIAL
ATIR101 has the potential of providing life-saving products to ~19,000 blood cancer patients a year, with a substantial expanding
primary market and complementary product trends. The Company estimates that approximately 35% of patients who are eligible
for, and who are in urgent need of, HSCT will not f nd a matching donor in time. A partially matched (haploidentical) family donor,
however, will be available to over 95%. Recent developments in cell-based immunotherapy have resulted in approached which
may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then
be eligible for curative HSCT. The product may benef t from market exclusivity up to 10 years post launch in the EU and 7 years in
the US due to its orphan drug status.
ATIR101 AIMS TO ADDRESS THE RISKS ANS LIMITATIONS OF HSCT
Current sequence of options physicians will consider
Haploidentical donor + ATIR101
IdenticalSibling(SIB)
MatchedUnrelated
(MUD)
Haploidenticaldonor +
Cyclophosphamide*
Umbilical Cord Blood
(UCB)
Time to collect stem cells < 1 month < 1-2 months 3-6 months < 1 month 2-3 months
Donor availability >95% ≤ 25% 45-55% >95% Limited
Risk of life-threatening GVHD Low Low Moderate - High Moderate - High Moderate
Need for immune suppressants No Yes Yes Yes Yes
Risk of opportunistic infections Low Moderate Moderate Moderate - High High
Risk of relapse in leukemia Low High Moderate - High High High
* Often referred to as the Baltimore protocol. Treatment method was established at the John Hopkins Hospital, Baltimore, USA. (Luznik et al., Biol Blood Marrow
Transplant. 2008)
Source table: Company information, CIBMTR, 2014 and Defin
e
d He al th, 2013 commi ssi oned by the Co mp any .
Survey included 50 US and 50 EU physicians.
Step 1 (Day 1–4)
Patient cells
inactivated
by radiation
Healthy
donor
Patient
Immune cells are collected and mixed
Certain T-cells from the donor are activated by the
presence of the ‘foreign’ patient cells. If not eliminated,
these cells would cause GvHD in the patient
Step 3 (Day 5)
Mixture is exposed to light.
TH9402 is activated by light, causing the
‘stained’ GvHD-causing T-cells to self-destruct
The remaining product is infused back
and helps rebuild their immune system
to f ght infections and eliminate
remaining tumor cells
Final Step - Infusion of ATIR101Step 2 (Day 5)
TH9402 is introduced.
TH9402 is retained ONLY in the GvHD-causing T-cells
FEBRUARY 2017
``
ATIR: remaining potent non-
alloreactive donor T-cells, infused ~30 days after
HSCT
Add TH9402*, which accumulates only in
activated T-cells (MDR pump is switched off in
activated T-cells)
*TH9402 – proprietary selective rhodamine derivative, modified to become cytotoxic under green light
Mix patient cells & haplo donor T-cells: alloreactive donor
T-cells become activated (Mixed
Lymphocyte Reaction)
Expose to green light: TH9402*, which
induces apoptosis, is activated & thus
alloreactive T-cells are killed
Protect: Retain protective T-cells to fight relapse and infections& Not attack: Reduce risk of GVHD by depleting alloreactive T-cells ex vivo
9
Phase 2 (007): potent T-cell product, yet low GVHD (1 yr)
• no acute grade III/IV
• 3 acute grade II (13%)
• 1 chronic (4%)
007: Haplo CD34+ plus single dose ATIR
• Open label single arm 2013-18• 23 AML/ALL patients receiving ATIR (MITT)• 4 sites Canada/EU • Dose 2 million cells/kg*
006: Haplo CD34+
• Historical observational cohort 2006-13• 35 patients, similar indications/sites• Protocol based on EMA scientific advice
Low GVHD due to ATIR
2 million cells/kg of potent T-cells:
increasing survival 3x, yet low GVHD**
No need for prophylactic immunosuppression
10* Non allodepleted donor lymphocyte infusion can cause severe GVHD at 10,000 cells/kg
Improved Overall Survival due to ATIR
CD34+ stem cells with ATIR
CD34+ stem cells without ATIR
3x
61%
20%
11
Phase 2 (007): relapse, GVHD & GRFS* vs. literature for PTCy
Comparison provided for illustrative purposes, based on literature comparison, NOT based on randomized controlled trials
* Defined as survival without chronic GVHD requiring immunosuppression, acute grade III/IV GVHD or relapse ** Ciurea 2015; Piemontese 2017, Solomon 2012, Ciurea 2012; Devillier 2016; Di Stasi 2014; Esquirol 2016; Sugita 2015*** Solh 2016 (Atlanta; DRI normalized GRFS 30%; n=128); McCurdy 2017 (Johns Hopkins; DRI normalized GRFS 38%; n=372)
**
***
Filed in EU & received ‘breakthrough’ in US, based on Phase 2
* Various hemato-oncology products (conditionally) approved by EMA based on Phase 2, e.g., Zalmoxis (MolMed, 36 patients, versus matched historical control), Blincyto, Venclexta, Bosulif
EMA (EU)
Marketing Authorization Application filed, potential (conditional) opinion Q4 2018
• ATMP certificate for quality and non-clinical data in 2015
• Pediatric Investigation Plan agreed
• Phase 2 and historical control accepted for filing and review*
• Day 120 questions submitted end Q1 2018
FDA (U.S.)
Regenerative Medicine Advanced Therapy designation received (same benefits as Breakthrough)
• Increased access to FDA (not limited to customary timepoints)
• Possibility for priority/rolling review of BLA
• Development support (program/endpoints)
12
Objectives: demonstrate superior clinical benefit and collect pharmacoeconomical data (cost, days in hospital, incidence of severe infections and quality of life)
Commenced Phase 3 Clinical Study
R
RandomizedControlled(1:1)
HSCT plus ATIR: CD34+ HSCT + single dose ATIR101
PTCy/Baltimore protocol: post-HSCT cyclophosphamide & immunosuppressant
Primary endpoint: GVHD-Free and Relapse-Free Survival (GRFS**)
195 patients* in U.S., Canada and EU
Aligned with FDA and regulators in EU; Enrolling patients
* 80% powered to detect 20% GRFS difference; 15% difference will be statistically significant; allowed under protocol to increase sample size; 245 pts would give 80% power to detect 18% difference** Survival without chronic GVHD requiring immunosuppression, acute grade III/IV GVHD or relapse
13
Kiadis key milestones and upcoming catalysts
14
2017
EMA submission of ATIR for marketing authorization approval ✔
First patient enrolled for ATIR Phase 3 ✔
Updates enrollment, regulatory, new clinical sites ✔
FDA Regenerative Medicine Advanced Therapy designation ✔
Secured own commercial manufacturing facility (lease) ✔
New management and supervisory board members ✔
2018
Completion of enrollment of second Phase 2 trial (CR-AIR-008) ✔
Submission of answers to EMA Day 120 questions (End Q1) ✔
Potential EU CHMP opinion, Q4
Updates Phase 2 data and Phase 3 enrollment
2019
Potential initial commercial launch ATIR in first of EU5 countries (H2)
Initiate trial with ATIR as adjunctive to PTCy
Potential interim read out Phase 3